Evolution of Bone Marrow Transplantation in Total Body Irradiation Study at the University of Cincinnati

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EVOLUTION OF BONE MARROW TRANSPLANTATION IN TOTAL BODY 1RRADIATION.STUDY AT THE UNIVERSITY OF CINCINNATI Because of radiation-induced hematologic depression; autologous Employing the method ofbone marrow storage was instituted in 1964. Kernick (Transfusion 2: 178-183, 1962) marrow was removed from the posterior iliac crest under local anesthesia, averaging approximately 500 cc in volde. .medium and stored at -83' centigrade after programmed temperature reduction 1' centigrade per minute. added,snd then the marrow was given intravenously, initially vithout filtration, at a rate of 50 to 60 cc. per minute. who received a marrow transfusion in our study, numbers 051 and 053, were infused with frozen marrow 24 and 19 days post irradiation respectively,at a time when the marrow sinusoids were relatively It was the mixed with Dsgood-glycerol Prior to infusion dextrose was The first two patients empty of precursor cells,with the expectation that there would be rare room for the transplant to take. Marrow viability in these - two procedures was 55% and 57%. Further details o f these two infusions can be f o m d on page 34 of our report to the Defense Atomic Support Agency, May 1, 1967 through April 30, 1968 in Table 5. Patient number 051 experienced mod,erate hemoglobinuria not seen in patient 053 after infusion. weeks post irradiation; hence it was impossible to distinguish spontaneow marrow recovery from successful marrow autotransfusion. Harrow was given in both cases 2 to 3 Because hemoglobinuria had been noted a triple filter systex was developed and marrow autotransplantation on patient 070, 077, 078, 087, 090, 091, 095, 098, 099, 107 and 111 have all been performed employing this filter sytem. The technique has been described in our report to

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the Defense Atomic Support Agency (DASA 01-C-69-0131) for Yay 1, 1970 through April 30, 1971, pages 19-42. In marrow transplsllts of patients 070, 077, and 078 the delay between t h e removal of marrow and transfusion was 11, 2 and 0 days 125,000 per cubic millimeter. but t h e white blood count dropped as low as 900,suggesting possible effectiveness of the technique for the first time. The platelet coat of patient 078 never fell below For the next 8patients the technique was therefore modified 80 that a larger volume of marrow (500 cc.) was removed from the patient under general anesthesia. and t h e marrow replaced intravenously on t h e same day as it was removed. Table 3 of the Defense Atomic Support Agency report May 1, 1970 through April 30, 1971 indicates the success attendant on t h e modification of this procedure. Furthermore, our patients now require hospitallz ation for4to5 days in total,after the first patient transplanted with our new technique (Patient 087) was followed in t h e Clinical Research Center, Cincinnati Children's Hospital, f o r over 6 weeks without any evidence of illness. The patient was then irradiated The three failures in the revised transplantation technique have been patient 090, 099 and 107. j cc ident unrelated toher tumor o r her radiotherapy. patients (099. 107) had had widespread radiotherapy which had affected the reticuloendothelial framework necessary for stem cell development, and preliminarg cell aspirates in alledgedly unirradiated areas, did appear hypocellular. n o m 1 granulocyte reserves. one of our marrow screening parameters, only because w e were given an incorrectly high body weight on which Patient 090 suffered a cerebrovasculer The letter two Patient 107 appeared t o possess

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to base our etiocholanolone dosage, thus falsely elevating the -marrow and granulocyte reserves. From this unfortunate experience ve now insist that a candidate for marrow autotransplantation have a normal iliac marrow aspirate histologically, a normal bone marrow scan employing technetium 99m sulfur colloid, and normal granulocyte reserves measured with etiocholanolone(after we weigh the patient)as At autopsy. patient 099,who died on day 31 post radiatio%had widespread carcinoma of the pancreas. her pancytopenia without any evidence of sepsis. indicators of normal marrow function. The marrow transplantation technique developed at this Medical Center has been further evaluated in two marrow allotransplantation attempte in two women dying of aplastic anemia with septicemia. In the first patient, transfused while she was in shock secondary to Gram-negative septicemia, there were no cardiovascular sequelae of the transplantation. but the patient died of her infecticn two hours after infusion of the marrow. no bone, fat, or fibrin emboli in the lungs. in shock secondary to Gram-negative septicemia, had impressive clinical improvement post-transplantation with normalization of body temperature and recovery from shock, but died from intracerebral hemorrhage on the 4th day post transplantation. Post mortem examination indicated - The second woman, also It should be noted that patient 111 has not been included in the analyses of marrow transplantation contalned in our DASA report cowring May 1, 1970 through April 30, 1971. because her marrow autotransplantation occurred May 19, 1971. do well however, and her hospitalization lasted only 4 days. This patient continues to